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Keywords = YbiA

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15 pages, 4425 KB  
Article
Specificity of DNA ADP-Ribosylation Reversal by NADARs
by Bara Cihlova, Yang Lu, Andreja Mikoč, Marion Schuller and Ivan Ahel
Toxins 2024, 16(5), 208; https://doi.org/10.3390/toxins16050208 - 28 Apr 2024
Cited by 12 | Viewed by 5194
Abstract
Recent discoveries establish DNA and RNA as bona fide substrates for ADP-ribosylation. NADAR (“NAD- and ADP-ribose”-associated) enzymes reverse guanine ADP-ribosylation and serve as antitoxins in the DarT-NADAR operon. Although NADARs are widespread across prokaryotes, eukaryotes, and viruses, their specificity and broader physiological roles [...] Read more.
Recent discoveries establish DNA and RNA as bona fide substrates for ADP-ribosylation. NADAR (“NAD- and ADP-ribose”-associated) enzymes reverse guanine ADP-ribosylation and serve as antitoxins in the DarT-NADAR operon. Although NADARs are widespread across prokaryotes, eukaryotes, and viruses, their specificity and broader physiological roles remain poorly understood. Using phylogenetic and biochemical analyses, we further explore de-ADP-ribosylation activity and antitoxin functions of NADAR domains. We demonstrate that different subfamilies of NADAR proteins from representative E. coli strains and an E. coli-infecting phage retain biochemical activity while displaying specificity in providing protection from toxic guanine ADP-ribosylation in cells. Furthermore, we identify a myxobacterial enzyme within the YbiA subfamily that functions as an antitoxin for its associated DarT-unrelated ART toxin, which we termed YarT, thus presenting a hitherto uncharacterised ART-YbiA toxin–antitoxin pair. Our studies contribute to the burgeoning field of DNA ADP-ribosylation, supporting its physiological relevance within and beyond bacterial toxin–antitoxin systems. Notably, the specificity and confinement of NADARs to non-mammals infer their potential as highly specific targets for antimicrobial drugs with minimal off-target effects. Full article
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